Background

The main etiologic factor responsible for melanocytic pigmentation of the oral mucosa in the white population is cigarette smoking. In his 1977 report, Hedin
[1] coined the term smoker's melanosis to describe this clinical condition.

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Pathophysiology

Smoker's melanosis may be due to the effects of tobacco smoke on melanocytes located in the lining epithelium of the oral mucosa. It has been shown that melanin may bind many substances, including a variety of drugs, and has a high affinity for nicotine. Studies have also found that nicotine and tobacco-specific compounds (N-nitrosamines and benzopyrene) may accumulate in melanin-containing human tissues and affect melanogenesis.
[2, 3, 4]

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Etiology

Smoker's melanosis is likely due to direct effects of tobacco smoke on the oral mucosa. Smoke is thought to cause changes in the mucosa through a combination of physical (heat) and/or chemical (nicotine and tobacco-specific compounds) effects. Melanin can bind to many different compounds, including nicotine and benzopyrene present in the tobacco smoke, and these substances can stimulate melanocytes to produce melanin. Multiple studies have found that the frequency and amount of mucosal pigmentation correlates to the number of cigarettes smoked per day.
[5, 6] Moreover, smoking for no more than one year is associated with a significant increase in the frequency of oral pigmentation. Individuals using smokeless tobacco or nicotine-containing gum do not develop this condition.

Epidemiology

Frequency

United States

No prevalence studies on smoker's melanosis are available in the United States.

International

In a Swedish study of 30,118 whites, 21.5% of tobacco smokers exhibited smoker's melanosis, whereas only 3% of nonsmokers had the lesion.
[5] The anterior facial gingivae was the most common site for smoker’s melanosis in that study.
[7] In a study of Thai subjects and Malaysian subjects, nearly all had physiologic pigmentation, but tobacco users had significantly more oral surfaces displaying pigmentation.
[8] A Nigerian study reported a prevalence of 0.52% of pigmented sites in nonsmokers and 6% among smokers. The buccal mucosa was the most common site for smoker's melanosis in that African study.
[9] A study of Turkish Army recruits revealed gingival pigmentation in 27.5% of smokers and 8.6% of those who never smoked.
[10]

Studies of soft-tissue lesions in the Middle East and India report a high prevalence of smoker’s melanosis and suggested more healthcare attention and community awareness programs are needed.
[11, 12, 13, 14, 15]

It appears that smoker’s melanosis may also occur in nonsmokers exposed to environmental tobacco smoke, as multiple studies have shown an increase in gingival pigmentation of children and young adults whose parents smoke.
[16, 17, 18] Since gingival melanin pigmentation is so easily noticeable, these studies suggest that the pigmentation can be used to educate parents in regard to the harmful effects of passive smoking in children and may be a strong motivation for quitting the habit.
[16, 17] Similarly, an Iranian study found an increase in gingival pigmentation in nonsmoker married women whose husbands were heavy smokers. Interestingly, the study found that the increase in pigmentation was amplified if those women lived in smaller houses (floor area <78m<sup>2</sup>).
[19]

Race

Although smoker's melanosis may be most evident in whites because of a lack of physiologic pigmentation in the oral mucosa in this population, the condition can affect both light- and dark-skinned individuals. It has been noted that in dark-skinned ethnic populations, the frequency of oral pigmentation and the number of pigmented mucosal surfaces are higher in individuals who smoke than in nonsmokers.
[8, 9] In a study of white subjects, oral melanin pigmentation was noted in 21.5% of smokers, while only 3% of nonsmokers showed similar pigmentation.
[5]

Sex

Females appear to be affected by smoker's melanosis more than males.
[1, 5] Investigators have suggested that there might be a synergism between female sex hormone and tobacco smoke. This explanation is supported by the increase in pigmentation (ie, melasma) seen in women who are pregnant or taking oral contraceptive pills and by in vitro studies demonstrating an increase in melanin synthesis by melanocytes treated with estrogen.
[20, 21]

Age

In a study of 30,118 individuals, the prevalence of the pigmentation was the highest in the group aged 24-35 years. The authors listed multiple explanations for the finding, such as the fact that a higher proportion of tobacco smokers was identified in that age group, the more frequent presence of dentures covering the mucosa in older age groups, and the decrease in melanocyte activity seen with age.
[5]

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Prognosis

Smoker's melanosis is not associated with mortality or morbidity. The prognosis of a patient with smoker's melanosis is excellent. Nevertheless, the numerous health risks associated with tobacco smoking should be discussed with the patient.